PubMed · 5913633
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H Boman. 1966-04-01. [Hypoglycemic coma during chlorporpamide therapy].. https://pubmed.ncbi.nlm.nih.gov/5913633/
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Solid dispersions (SDs) of chlorpropamide were prepared by the solvent deposition technique using two grades of microcrystalline cellulose as carrier materials with different ratios of drug to carrier. The dissolution rate of chlorpropmide from the SDs was carried out at two physiological pH values of 1.1 and 7.25 simulating gastric and intestinal environments. The dissolution was dependent on the grade, the ratio of drug to carrier and pH. The higher dissolution was observed for more hydrophilic grade of the carrier as well as the higher ratio of carrier to drug. At the higher pH the drug dissolved much faster than the lower pH. X-ray diffraction showed some reduced drug crystallinity in SDs whereas infrared spectroscopy revealed no drug interactions with solvent and the carriers. The enhanced dissolution was attributed to the reduced drug crystallinity, decreased particle size, increased wettability and reduced aggregation of the hydrophobic drug particles. A novel model denoted as reciprocal powered time model with its theoretical justification was employed to analyze the dissolution data and proved to be superior to commonly used models for the analysis of the data. There was a quantitative relation between the model parameter and the ratio of carrier to drug which could be of value in dissolution rate prediction.
The effect of pressure up to 5.5GPa on a dry powder sample of chlorpropamide (4-chloro-N-((propylamino)-carbonyl)-benzenesulfonamide), form-A (sp. gr. P2(1)2(1)2(1), a=9.066A, b=5.218A, c=26.604A), was studied in situ in a Merrill-Bassett diamond anvil cell using high-resolution X-ray powder diffraction (a synchrotron radiation source at SNBL ESRF, Grenoble). No evidence of the polymorphic transformation of chlorpropamide form-A to form-C was observed. The A-C polymorphic transition on tabletting previously reported by is therefore likely to be due to local heating effects. Similarly, the phase transitions of form-A reported by to be induced by pressure applied to a sample in its saturated ethanol solution (at 0.9 and at 2.0GPa) would appear to be solvent-mediated. In the dry sample, a phase transition may be supposed to occur at pressures above 4GPa, but this requires further studies.
An analytical, non-destructive method using parallel-beam transmission powder X-ray diffractometry (PXRD) is presented for in situ whole compact detection and quantification of solid-state phase transformations in powder compacts. Accurate quantification of analyte in intact compacts using PXRD requires a mathematical correction prior to interpolation of calibration data to account for sample differences that result as a function of pressure; namely, compact thickness and solid fraction. Chlorpropamide is examined as a model system, selected because of its susceptibility to polymorphic transformations when consolidated using moderately low pressures. The results indicate that quantification of the transformed phase of chlorpropamide without corrections for solid fraction and thickness, underestimates the extent of transformation by 2.4%. Although the magnitude of the correction for this particular system of polymorphs is small, more significant values are expected for other compounds, particularly those with sufficient compactibility to allow the formation of low solid fraction calibration samples.